Platelet aggregation and
adenosine triphosphate (
ATP) secretion in response to
arachidonic acid (10 microM) or
collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage
aspirin (3.5 mg/kg of
body weight, PO, q 12 h for 7 treatments) or with
CGS 12970, a specific
thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of
arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either
aspirin or
CGS 12970. Treatment with
CGS 12970 or
aspirin significantly (P less than 0.001) decreased platelet
ATP secretion in response to
arachidonic acid, compared with baseline values; however
ATP secretion in
aspirin-treated dogs was significantly (P less than 0.01) less than
ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and
aspirin- or CGS 12970-treated dogs in response to
collagen as an aggregant, however,
collagen-induced platelet
ATP secretion was significantly (P less than 0.001) decreased in dogs treated with
aspirin, compared with control values and values from dogs treated with
CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of
CGS 12970/kg, dose-dependent inhibition of
arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)